Neuron-related blood inflammatory markers as an objective evaluation tool for major depressive disorder: An exploratory pilot case-control study

Nobuki Kuwano, Takahiro A. Kato, Masato Mitsuhashi, Mina Sato-Kasai, Norihiro Shimokawa, Kohei Hayakawa, Masahiro Ohgidani, Noriaki Sagata, Hiroaki Kubo, Takeshi Sakurai, Shigenobu Kanba

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)


Background: Neuroinflammation is suggested to be a crucial factor in the pathophysiology of major depressive disorder (MDD). Analysis of neuron-derived exosomes (NDE) in peripheral blood has recently been highlighted to reveal the pathophysiology of brain diseases without using brain biopsy. Currently, human NDE studies require a considerable amount of peripheral blood to measure multiple substances inside exosomes. Previously, NDE-based clinical studies focusing on MDD have not been reported. Methods: As an exploratory pilot case-control study between healthy controls (HC) and drug-free MDD patients (each; N = 34), we searched for NDE-related blood biomarkers with a small amount of peripheral blood using a novel sandwich immunoassay between anti-neuron antibody and antibodies against CD81 (an exosome marker) and against other proteins related to neuroinflammation and synaptic functions. Results: Most neuron-related blood biomarkers had moderately to strongly positive correlation with CD81 (NDE), thus we normalized the above biomarkers by CD81 (quantity of each biomarker/CD81) to predict NDE-related blood substances. Interleukin 34 (IL34)/CD81 levels were significantly higher in MDD group compared to HC group. Synaptophysin (SYP), SYP/CD81, and tumor necrosis factor receptor 1 (TNFR1)/CD81 were positively correlated with severities of depression and/or various sub-symptoms. Limitations: We did not actually extract NDE from peripheral blood. Conclusions: Using a small amount of peripheral blood, we have successfully detected possible NDE-related blood biomarkers. This is the first study to suggest that not only SYP and TNFR1 but also IL34 are important blood biomarkers for patients with MDD. Further studies are warranted to evaluate the present study.

Original languageEnglish
Pages (from-to)88-98
Number of pages11
JournalJournal of Affective Disorders
Publication statusPublished - Nov 2018

All Science Journal Classification (ASJC) codes

  • Clinical Psychology
  • Psychiatry and Mental health


Dive into the research topics of 'Neuron-related blood inflammatory markers as an objective evaluation tool for major depressive disorder: An exploratory pilot case-control study'. Together they form a unique fingerprint.

Cite this